rs1141608
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000651111.1(ENSG00000241489):c.-196C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,165,083 control chromosomes in the GnomAD database, including 54,181 homozygotes. There are 119,286 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
ENST00000651111.1 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IDS | NM_000202.8 | c.438C>T | p.Thr146Thr | synonymous_variant | Exon 4 of 9 | ENST00000340855.11 | NP_000193.1 | |
IDS | NM_001166550.4 | c.168C>T | p.Thr56Thr | synonymous_variant | Exon 4 of 9 | NP_001160022.1 | ||
IDS | NM_006123.5 | c.438C>T | p.Thr146Thr | synonymous_variant | Exon 4 of 8 | NP_006114.1 | ||
IDS | NR_104128.2 | n.607C>T | non_coding_transcript_exon_variant | Exon 4 of 9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENSG00000241489 | ENST00000651111.1 | c.-196C>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 9 of 14 | ENSP00000498395.1 | |||||
IDS | ENST00000340855.11 | c.438C>T | p.Thr146Thr | synonymous_variant | Exon 4 of 9 | 1 | NM_000202.8 | ENSP00000339801.6 | ||
ENSG00000241489 | ENST00000651111.1 | c.-196C>T | 5_prime_UTR_variant | Exon 9 of 14 | ENSP00000498395.1 |
Frequencies
GnomAD3 genomes AF: 0.312 AC: 34181AN: 109470Hom.: 4371 Cov.: 22 AF XY: 0.294 AC XY: 9358AN XY: 31862
GnomAD3 exomes AF: 0.275 AC: 50217AN: 182867Hom.: 5441 AF XY: 0.273 AC XY: 18400AN XY: 67351
GnomAD4 exome AF: 0.347 AC: 366356AN: 1055561Hom.: 49814 Cov.: 25 AF XY: 0.328 AC XY: 109916AN XY: 335471
GnomAD4 genome AF: 0.312 AC: 34176AN: 109522Hom.: 4367 Cov.: 22 AF XY: 0.294 AC XY: 9370AN XY: 31922
ClinVar
Submissions by phenotype
not specified Benign:4
- -
- -
- -
- -
not provided Benign:4
- -
- -
- -
Variant summary: The IDS c.438C>T (p.Thr146Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 24360/87524 control chromosomes (including 2605 homozygotes and 9302 hemizygotes) at a frequency of 0.2783237, which is approximately 96 times the estimated maximal expected allele frequency of a pathogenic IDS variant (0.0028868). Thus this variant is a common polymorphism found in the general population. In addition, multiple clinical diagnostic laboratories have classified this variant as benign and the variant is considered a common polymorphism in the literature. Taken together, this variant is classified as Benign. -
Mucopolysaccharidosis, MPS-II Benign:4
- -
- -
- -
- -
Inborn genetic diseases Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at